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This study compares the potential benefit of fifth metatarsal head resection versus standard conservative treatment of plantar ulcerations in people with diabetes mellitus. Using a retrospective cohort model, we abstracted data from 40 patients (22 cases and 18 controls) treated for uninfected, nonischemic diabetic foot wounds beneath the fifth metatarsal head. There were no significant differences in sex, age, duration of diabetes mellitus, or degree of glucose control between cases and controls. Patients who underwent a fifth metatarsal head resection healed significantly faster (mean ± SD, 5.8 ± 2.9 versus 8.7 ± 4.3 weeks). Patients were much less likely to reulcerate during the period of evaluation in the surgical group (4.5% versus 27.8%). The results of this study suggest that fifth metatarsal head resection is a potentially effective treatment in patients at high risk of ulceration and reulceration. (J Am Podiatr Med Assoc 95(4): 353–356, 2005)